Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function - Full Text View

Purpose

The purpose of this study is to assess whether a dosing adjustment is needed in patients with renal impairment.

Condition	Intervention	Phase
Human Immunodeficiency Virus (HIV) Infection	Drug: Maraviroc Drug: Ritonavir Drug: Saquinavir	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label, Parallel Group, Single And Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Dialysis HIV/AIDS

Drug Information available for: Saquinavir Saquinavir mesylate Ritonavir Maraviroc

U.S. FDA Resources

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:

Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) measured in nanograms * hour divided by milliliters (ng*hr/mL).
AUCtau [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
AUCtau: area under the plasma concentration-time profile from time zero to the end of the dosing interval (tau); measured in nanograms * hours divided by milliliters (ng.hr/mL).
Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).

Secondary Outcome Measures:

Plasma Protein Binding [ Time Frame: 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1 ] [ Designated as safety issue: No ]
Percent protein binding (protein unbound maraviroc (MVC) fraction [percent free]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.
Area Under the Time Curve From 0 to Infinity (AUCinf) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 ] [ Designated as safety issue: No ]
Area under the plasma concentration-time profile from time zero to the time infinate in subjects who received single dose treatment; measured in nanograms * hour divided by millilters (ng*hr/mL).
Time of First Occurrence (Tmax) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.
Half-life (t1/2) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
Elimination half-life (t1/2) measured in hours: time required for half the quantity of maraviroc to be metabolized or eliminated by normal biological processes.
Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function [ Time Frame: Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
Renal clearance (CLR) measured in milliliters per minute (mL/min).
Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae [ Time Frame: Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).
Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD [ Time Frame: Before dialysis ] [ Designated as safety issue: No ]
CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure [ Time Frame: Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up ] [ Designated as safety issue: No ]
Number of subjects with absolute values of supine systolic blood pressure (BP) measured in millimeters of mercury (mm/Hg), range: <90 mmHg; and supine diastolic blood pressure, range: <50 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine systolic BP ≥ 30 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine diastolic BP ≥ 20 mmHg.
Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute [ Time Frame: Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up ] [ Designated as safety issue: No ]
Number of subjects with pulse rate < 40 beats per minute (BPM), number of subjects with pulse rate > 120 BPM.
Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals [ Time Frame: Normal renal function: screening, Day -3 and Day -1; normal renal function, mild and moderate RI: Day 7 to Day 9 and follow-up; severe RI: screening, Day 1, Day 3, Day 4, and follow-up; ESRD: screening, Day 1, Day 3, Day 4, and follow-up ] [ Designated as safety issue: No ]
Single 12-lead ECG: number of subjects with maximum QTC interval, maximum QTCB interval (Bazett's correction), and maximum QTCF interval (Friderica's correction) measured in milliseconds (msec); range: 450 to <480 msec, 480 to <500 msec, and >500 msec. Maximum QTC interval increase from Baseline; citeria: change = ≥ 30 msec to < 60 msec, and change = ≥ 60 msec.

Enrollment:	30
Study Start Date:	July 2008
Study Completion Date:	November 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Healthy Subjects Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir	Drug: Maraviroc Maraviroc 300 mg (150 mg x 2 tablets) x single dose Drug: Maraviroc Maraviroc 150 mg tablet twice daily x 7 days Drug: Ritonavir Ritonavir 100 mg capsule twice daily x 7 days Drug: Saquinavir Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Experimental: Mild Renal Impairment Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)	Drug: Maraviroc Maraviroc 150 mg tablet once daily x 7 days Drug: Ritonavir Ritonavir 100 mg capsule twice daily x 7 days Drug: Saquinavir Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Experimental: Moderate Renal Impairment Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)	Drug: Maraviroc Maraviroc 150 mg tablet once every 48 hours x 7 days Drug: Ritonavir Ritonavir 100 mg capsule twice daily x 7 days Drug: Saquinavir Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Experimental: Severe Renal Impairment Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)	Drug: Maraviroc Maraviroc 300 mg (150 mg x 2 tablets) x single dose
Experimental: ESRD on Hemodialysis Subjects with End Stage Renal Impairment receiving Hemodialysis(Creatinine Clearance <30 mL/min) (I) Maraviroc single dose one hour following completion of hemodialysis, followed by (II) Maraviroc single dose three hours prior to start of hemodialysis	Drug: Maraviroc Maraviroc 300 mg (150 mg x 2 tablets) x single dose one hour following completion of hemodialysis Drug: Maraviroc Maraviroc 300 mg (150 mg x 2 tablets) x single dose three hours prior to start of hemodialysis

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Stable Renal Function defined as ≤20% (25% for normal renal function) difference between 2 measurements of serum creatinine obtained on 2 occasions separated by at least 2 weeks.
Body Mass Index (BMI) of approximately 18 to 40 kg/m2 inclusive.
Total body weight >50 kg (110 lbs).
Male or female subjects between the ages of 18 and 85 years.

Exclusion Criteria:

Subjects with acute renal disease and/or history of renal transplant.
Supine BP at Screening ≥160 mm Hg systolic or ≥95 mm Hg diastolic.
Supine BP at Screening ≤80 mm Hg systolic or ≤40 mm Hg diastolic.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00717067

Locations

Germany
Pfizer Investigational Site
Berlin, Germany, 10117
Pfizer Investigational Site
Muenchen, Germany, 81241

Sponsors and Collaborators

ViiV Healthcare

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00717067 History of Changes
Other Study ID Numbers:	A4001075
Study First Received:	July 15, 2008
Results First Received:	November 16, 2009
Last Updated:	November 10, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:

maraviroc, pharmacokinetics, renal impairment

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Saquinavir

Ritonavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 13, 2013